tbuckley/cabot-search huggingface dataset:
Clinicopathologic characteristics and outcomes for patients with <i>KRAS</i> G12D-mutant non-small cell lung cancer (NSCLC).
Authors: Alissa Jamie Cooper, Alona Muzikansky, Jochen K Lennerz, Mari Mino-Kenudson, Yin P Hung, Zofia Piotrowska, Ibiayi Dagogo-Jack, Lecia V. Sequist, Jessica Jiyeong Lin, Justin F. Gainor, Rebecca Suk Heist
Journal: Journal of Clinical Oncology (2022)

e21024 Background: Co-occurring mutations in KRAS-mutant NSCLC are associated with discrete biological properties and modulate therapeutic susceptibilities. As G12D-specific inhibitors are expected to enter the clinic, we sought to define the clinicopathologic characteristics and outcomes of patients (pts) with KRAS G12D-mutant NSCLC. Methods: This was a retrospective single-institution study. Pts with NSCLC and KRAS G12D mutations detected by the Massachusetts General Hospital SNaPshot next-generation sequencing assay were identified. Clinical and pathologic characteristics, including co-mutation status and survival outcomes, were collected by chart review. Results: Among pts who underwent SNaPshot testing between May 2014 and August 2021, 665 had cancers that were positive for KRAS G12D, of whom 107 (16.1%) had NSCLC. Most common histology was adenocarcinoma (93, 86.9%). PD-L1 level was &lt; 1% in 24 (22.4%), 1-49% in 19 (17.8%), &gt; 50% in 13 (12.2%), and not assessed in 51 (47.7%). Co-occurring mutations were frequent: 17 NSCLCs had co-occurring STK11 mutations (15.9%), 36 (33.6%) TP53 mutations, and 11 (10.3%) SMARCA4 mutations, of which 2 were truncating. Genetic alterations were detected in a variety of other genes including in the RTK/RAS/MAPK (20, 18.7%), PI3K/AKT/mTOR (12, 11.2%), cell-cycle (17, 15.9%), and WNT (11, 10.3%) pathways. Among 58 tumors with KEAP1 mutation testing, 10 (17.2%) were positive. 75 (70.1%) pts had metastatic disease, including 51 pts who had metastatic disease at initial diagnosis. CNS metastases were present in 27 (36.0%) pts, including 14 pts with CNS metastases at initial diagnosis. Among the 57 pts with metastatic disease who received first-line therapy, 28 (49.1%) received platinum-based chemotherapy, 17 (29.8%) immunotherapy alone, and 12 (21.1%) platinum chemotherapy plus immunotherapy. Median PFS in pts treated with first-line therapy was 4.0 months (95% CI 2.1– 5.7) and median OS 14.3 months (95% CI 8.1 – 27.4). When stratified by co-mutation status, pts with STK11 mutations had significantly worse outcomes than STK11-wild-type (median PFS: 1.2 months vs 4.8 months, p = 0.0165; median OS: 4.3 months vs 21.6 months, p = 0.0015), whereas TP53 exerted no influence. Conclusions: Co-occurring mutations were common in pts with KRAS G12D-mutant NSCLC. Outcomes were poorer for KRAS G12D/ STK11 pts, whereas co-occurring TP53 did not impact survival. Clinical trials examining G12D inhibitors should stratify by STK11.
Individualized risk prediction of metastatic recurrence in patients candidate to radical prostatectomy: A new model using clinical, mri and mri-guided biopsy parameters
Authors: T. Bommelaere, A. Villers, P. Puech, G. Ploussard, J. Labreuche, E. Drumez, X. Leroy, J. Olivier
Journal: European Urology (2022)
miR-150 expression in breast cancer attracts and activates immune cells, and is associated with better patient outcome.
Authors: Masanori Oshi, Aparna Maiti, Rongrong Wu, Yoshihisa Tokumaru, Vijayashree Murthy, Li Yan, Takashi Ishikawa, Itaru Endo, Nitai Hait, Kazuaki Takabe
Journal: Journal of Clinical Oncology (2022)

570 Background: MicroRNA (miRNA) epigenetically regulate a large number of cancer-related genes and is known as a key player in cancer biology. MiR-150 promote cancer cell proliferation, migration, and invasion. However, there has been no study that investigated the role of miR-150 in the tumor microenvironment (TME) of breast cancer patients. Methods: Total of 1,961 breast cancer patients from multiple independent large cohorts were analyzed. These observational results were validated by in vitro experiments. Lymphocyte attraction was assessed using Transwell system. Results: miR-150 expression was the highest in triple negative breast cancer (TNBC) among subtypes and correlated with Nottingham histological grade (all p&lt;0.001). A high miR-150 was significantly associated with better overall survival (OS) in both METABRIC and TCGA cohorts regardless of subtypes (all p&lt;0.05 except for TNBC in TCGA). MiR-150 expression was strongly correlated with Hallmark immune-related gene sets (Allograft rejection, IL6 signaling, IFN-γ response, Inflammatory response, IL2 signaling, and apoptosis), with cytolytic activity, with infiltration of CD8+ T cells, CD4+ memory T cells, and dendritic cells, as well as with gene expressions of major immune checkpoint molecules (PD-1, CTLA4, IDO1, TIGIT, BTLA, and LAG3), consistently in both METABRIC and TCGA cohorts (all r&gt;0.65, p&lt;0.01). Unexpectedly, overexpression of miR-150 by mimic did not increase growth, migration, nor invasion of neither MDA-MB231 or BT-549 breast cancer cell lines. On the other hand, overexpression of miR-150 in either MDA-MB231 or BT-549 significantly increased attraction of lymphocyte cell line (Jurkart cells), which was abolished by addition of miR-150 inhibitor. By comparing the gene expression profile between miR-150 overexpressed and control cells, we found that many inflammation related gene sets including NF-kB signaling that enhance cell migration was enriched to miR-150 overexpressed cells, implicating that is how miR-150 high cells attract lymphocytes to TME. Conclusions: miR-150 expression is associated with immune cell infiltration and immune response, as well as with better survival in breast cancer patients. Overexpression of miR-150 in breast cancer cells did not promote cancer cell proliferation, migration, nor invasion; however, increased attraction of lymphocytes. Multiple inflammation-related genes were expressed higher in miR150 overexpressed MDA-MB231.
Palliative care utilization and mortality in patients who received inpatient chemotherapy.
Authors: Justine Anderson, Shivani Handa, Giulia Petrone, Nobel Chowdhury, Deukwoo Kwon, Aarti Sonia Bhardwaj, Priya Jain, Cardinale B. Smith, Natalie S Berger
Journal: Journal of Clinical Oncology (2022)

e24074 Background: Early integration of palliative care (PC) into advanced cancer care has been shown to improve quality of life and prognostic understanding. However, there is a paucity of data on utilization of inpatient PC consultation and survival outcomes in patients (pts) receiving inpatient chemotherapy (IC). Methods: A retrospective review was performed at a single academic center of pts receiving IC between Jan 2016 and Dec 2017. We evaluated utilization of PC services, reasons for consult, code status, disposition, and 60-day mortality. Descriptive statistics and odds ratios (OR) were estimated from logistic regression models with mixed-effect, taking into account correlations from multiple admissions per patient. Cumulative incidence plot and Cox proportional hazard regression models were used to assess the association between mortality and study covariates. Results: Of 880 admissions, 733 (83%) were hematologic malignancies (HM) and 147 (17%) were solid tumors (ST). PC consults were more likely in ST than HM (OR 3.19, 95% CI 1.85 - 5.50) and for KPS ≤50% (OR 22.20, 95% CI 11.51- 42.79). Of 159 PC consults, 91 (57%) were for pain and 25 (16%) for goals of care. 66 pts (10%) who received IC died within 60 days of admission, 44 (67%) HM and 22 (33%) ST (p = 0.002). In pts who died within 60 days, 63% had PC consult. Median time from admission to PC consult was 2 days for ST and 9 for HM. Of those with PC consult, 40% had a change from full code to DNR/DNI and were more likely to have a health care proxy (HCP) assigned (OR 7.31, p = 0.001). PC consults were also associated with significantly higher odds of discharge to hospice (OR 10.52, 95% CI: 4.3-25.6; p = &lt; 0.0001; Table). Mortality risk was higher in those admitted for symptoms/complications related to their disease or with progression (HR 3.24, 95% CI (2.50-4.19), p &lt; 0.001) and in those with advanced stage disease: Stage 3 (p = 0.033); Stage 4 (p = 0.0003). Of the pts who died within 60 days, 33 (50%) died during the admission and 24 (36%) in hospice. Conclusions: Significant 60-day mortality after receiving IC is consistent with aggressive end-of-life care. Pts with ST and those with poor performance status more frequently utilized inpatient PC services; however, there is opportunity to increase utilization amongst pts with HM and introduce PC earlier in the inpatient clinical course. PC consultations improve advanced care planning with appropriate transitions in code status, HCP assignments, and discharge to hospice.[Table: see text]
Morphometric, histological and immunohistochemical study of the His bundle in humans and other animal species
Authors: FA Gomez-Torres, C Rios Navarro, M Ortega, V Bodi, A Ruiz-Sauri
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637 and CIBERCV16/11/00486) and Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). Introduction The His bundle is responsible for transmitting the electrical impulse from the atria to the ventricles where it connects with the Purkinje cells in both normal and abnormal hearts. The aim of this study was to perform a morphometric analysis of His bundle characteristics of in humans, dogs, horses and pigs and compare them in these studied species. Methods We analyzed five hearts of human male adults, five male pig hearts, five hearts from male horses and five hearts of male dogs. Histological sections of 5 μm thickness were obtained and stained with hematoxylin–eosin and Masson’s trichrome; the desmin and periodic acid–Schiff methods were also used for precise identification of cells. Results The His bundle was found to be longer in horses (2.85 ± 1.02 mm) and pigs (1.77 ± 0.9 mm) than in dogs (1.53 ± 0.8 mm) or humans, in which it was shortest (1.06 ± 0.6 mm). The area and diameters in His bundle cells, were significantly larger in pigs and horses than in humans (p &amp;lt; 0.001) or dogs (p &amp;lt; 0.001). We found two organizational patterns of His bundle components: group I, with large cells and a high amount of collagen fibers in ungulates (pigs and horses); and group II, with smaller cells and lower abundance of collagen fibers in humans and dogs. Conclusions Determining morphometrically cell size variations in the His bundle allows us not only to identify this bundle by histological or anatomical location but also to differentiate these cells from others such as nodal or Purkinje cells. Our analysis revealed that His bundle cells have discrete identities based on their morphometric and histological characteristics.
Comprehensive landscape of tumor angiogenesis via integrating RNA sequencing and three-dimensional microphysiological system.
Authors: Jihoon Ko, Sujin Hyung, Minae An, Se Hoon Park, Seung Tae Kim, WonKi Kang, Noo Li Jeon, Jeeyun Lee
Journal: Journal of Clinical Oncology (2022)

e16058 Background: The prognosis of gastric cancer (GC) patients with peritoneal metastasis with malignant ascites is very poor. We developed an in vitro tumor angiogenesis platform “TumorAngioChip” to reproduce tumor angiogenesis in 45 gastric cancer patients and mapping their angiogenesis characteristics. This platform, which can predict the features of tumor angiogenesis and drug responsiveness in patient’s samples, opens up potential for a variety of combination therapies, including ramucirumab. Methods: We built a PDC library for the study based on samples of 45 GC patients receiving treatment at Samsung Medical Center. For all patient samples, whole exome and transcriptome sequencing was performed for subtype clustering. TumorAngioChip was fabricated by design prototyping through 3D printing and mass production through injection molding. Patient-derived tumor angiogenesis reconstructed on TumorAngioChip was analyzed using an algorithm for morphological image processing of 3D images obtained through confocal microscopy. Results: Of 45 GC patients, we investigated TumorAngioChip analysis and transcriptome sequencing to classify them as KDR-High (N = 24) and KDR-Low (N = 21) ( P = 4.481e-08, Wilcoxon signed-rank test). In the TumorAngioChip–patient mapping analysis, we clearly demonstrated that GC patients with high KDR level regardless to their GC TCGA subtype had high index of tumor-induced angiogenesis and cancer invasiveness measured by TumorAngioChip ( KDR-High vs. KDR-low group; mean sprouting length: 1.455 × 10 3 vs. 0.946 × 10 3 , respectively, P &lt; 0.0001; vessel density: 3.470 vs. 2.637, respectively, P &lt; 0.0001; sprouts number: 219 vs. 111, respectively, P &lt; 0.0001; vessel total length: 4.931 × 10 4 vs. 3.919 × 10 4 , respectively, P = 0.0011). Conclusions: This study is the first attempt to elucidate cancer angiogenesis in large-scale GC patients via a microfluidic-based in vitro system. By integrating transcriptome sequencing and TumorAngioChip-based 3D morphological image processing, we demonstrated tumor angiogenesis mapping for GC patients and further revealed the benefits of ramucirumab in individual patients. The application of TumorAngioChip shows its potential as a novel preclinical drug screening platform to identify effective angiogenesis inhibitors reflecting TME for the first time.
The Oncotype DX Genomic Prostate Score® assay is associated with time to distant metastasis and prostate cancer death after external beam radiation therapy in localized prostate cancer: A retrospective study
Authors: S. Freedland, M.J. Boyer, J. Janes, J. Bennett, V.M. Thomas, A.M. De Hoedt, J. Abran, T. Aboushwareb, J.K. Salama
Journal: European Urology (2022)
LGG-41. The clinical and molecular landscape of gliomas in adolescents and young adults
Authors: Julie Bennett, Liana Nobre, Javal Sheth, Scott Ryall, Karen Fang, Monique Johnson, Logine Negm, Jiil Chung, Martin Komosa, Nuno M Nunes, Mary Jane Lim Fat, James Perry, Arjun Sahgal, Jay Detsky, Eric Bouffet, Lili Naz-Hazrati, Peter Dirks, Birgit Ertl-Wagner, Paul Kongkham, Gelareh Zadeh, Warren Mason, Seth Climans, Michael Cusimano, Sunit Das, Andrew Gao, Derek Tsang, Lananh Nguyen, Normand Laperriere, Julia Keith, David Munoz, Uri Tabori, Cynthia Hawkins
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: Gliomas in adolescents and young adults (AYA) are commonly treated with a standard chemo-radiation approach based on data from adults. The clinical impact of paediatric-type alterations in these tumours is unknown. METHODS: We compiled a multi-institutional cohort of patients diagnosed with glioma between 15-39.9 years over 20 years. Complete molecular analysis, therapeutic data and outcome was collected. For specific alterations, analysis included patients aged 0-39.9 years. RESULTS: A total of 1900 patients with 876 AYA gliomas were included. Ongoing analysis reveals genetic alterations in 95% of available tumours. IDH-mutant tumours account for only 53%, while paediatric-type mutations were found in 35% of AYA tumours with IDH-WT GBM accounting for the remaining 12%. The most common paediatric alterations in AYAs included BRAF p.V600E (11%) and FGFR alterations (6%) while BRAF fusions, H3 p.K27M and H3.3 p.G34R were rarely observed (4%, 4% and 1% respectively). BRAF fused tumours with non-canonical binding partners were enriched in AYAs. Analysis of BRAF-V600E gliomas between ages 0-40 revealed increased tendency for malignant tumours in patients &amp;gt;20 years suggesting malignant transformation possibly due to higher rate of secondary hits including TP53, CDKN2A and ATRX mutations. This resulted in worse overall-survival for AYA patients with BRAF-V600E glioma when compared to children under 20 years (p=0.0032). Ten-year OS of 100%, 90% and 95% was seen for BRAF fused, BRAF-V600E and FGFR-altered AYA low grade glioma respectively, compared to 14% and 25% for BRAF-V600E and FGFR-altered high grade glioma. In contrast, continuous decline was observed in the IDH-mutant gliomas with 10-year OS of 50% which declined to 29% at 15 years. CONCLUSIONS: Gliomas in AYA are enriched for paediatric-type alterations with distinct molecularly-based outcomes. As these tumours carry different outcomes than childhood glioma and may respond to targeted inhibitors, AYA gliomas would benefit from comprehensive diagnostic and therapeutic approaches.
Prognostic value of hPG<sub>80</sub> (circulating progastrin) in IDH-wild type glioblastoma treated with radio-chemotherapy.
Authors: Ludovic Doucet, Axel Cailleteau, Loig Vaugier, Carole Gourmelon, Mathilde Bureau, Celine Salaud, Vincent Roualdes, Edouard Samarut, Maud Aumont, Morgan Zenatri, Delphine Loussouarn, Veronique Quillien, Francois Bocquet, Lea Payen-Gay, Younes Mahi, Alexandre Prieur, Marie Robert, Jean-Sebastien Frenel
Journal: Journal of Clinical Oncology (2022)

2049 Background: hPG 80 (circulating progastrin) is a protein secreted by many cancer types, playing a role in tumorigenesis by regulating cancer stem cells, angiogenesis, proliferation/differentiation and decreasing apoptosis. hPG 80 is detectable in plasma of cancer patients and previous studies have shown its prognostic role in various cancers. Given the lack of circulating biomarker in glioblastoma, we evaluated the prognostic value of plasma hPG 80 in patients with IDH wild type glioblastoma Methods: This multicentric retrospective study included IDHwt glioblastoma patients treated with standard radio-chemotherapy. The ELISA DxPG80.lab kit (Biodena Care, Lausanne, Switzerland) was used to measure hPG80 levels after surgery with a detection threshold of 1 pM in all plasma EDTA samples according to the manufacturer’s instruction. The prognostic impact of hPG 80 was evaluated on patient’s progression-free survival (PFS) and overall survival (OS). Results: We included 70 patients (38 males /32 women) with a median age of 64 years (Range 19 - 84). Karnofsky index was &gt; 70% in 52 (91%) of 57 evaluable patients. Tumor biopsy (B), partial resection (PR), complete resection (CR) were performed in 22, 25 and 23 patients respectively. MGMT promotor was methylated in 22 (40%) of the 55 evaluable patients. After surgery, hPG 80 was detected in 48 (69%) patients (hPG80+) with a median concentration of 9.52 pM (IQR 5.21 - 21.20). Complete surgery was associated with undetectable levels of hPG80 (52% (CR) vs 28% (PR) vs 14% (B), p = 0.006) and lower concentration if hPG80+ (CR: 5.8 pM [IQR 1.92 - 11.38] vs PR: 12.84 pM [IQR 8.09 - 37.09]; p = 0.04 vs B: 9.86 pM [IQR 4.66 - 21.63]; p = 0.16). With a median follow-up of 39 months (22.4-NR), 86% of patients had progressed and 70% had died. In univariate analysis, hPG 80 positivity was associated with PFS (5.6m vs 8.5m, p = 0.053) and OS (14.5 vs 22m, p = 0.04) in hPG 80 + vs hPG 80 - patients respectively. hPG 80 + patients with complete surgery had worse median OS than hPG 80 - patients (14.5 vs 22.0 m; p = 0.051 respectively. Cox proportional hazards model did not fit for covariate analysis. Conclusions: Our findings show that hPG 80 could serve as a new circulating prognostic biomarker in IDHwt glioblastoma patients treated with radio-chemotherapy. Further explorations are ongoing in larger cohorts including longitudinal evaluation during the course of the disease.
A multiplexed immunohistochemical consecutive staining on single slide (MICSSS) analysis of the immune microenvironment of bile duct cancers (BDC) pre and post neoadjuvantchemotherapy (NACT).
Authors: Sirish Dharmapuri, Rafael Cabal, Giorgio Ioannou, Sinem Ozbey, John Paulsen, Celina Ang, Umut Sarpel, Max W. Sung, Peter Kozuch, Myron E. Schwartz, Deirdre Jill Cohen, Sacha Gnjatic, Sofya Pintova
Journal: Journal of Clinical Oncology (2022)

e16151 Background: NACT is increasingly being used in the management of locally advanced BTC. Emerging evidence suggests a potential key contributing role of tumor infiltrating immune cells in the prognosis &amp; response to therapy. We set out to characterize immune modulation of tumor immune microenvironment composition in BTC following NACT. Methods: Patients (pts) with locally advanced BTC who underwent a diagnostic biopsy, then NACT followed by resection between 2014 &amp; 2018 were identified &amp; consented after IRB approval. MICSSS, a sample-sparing chromogenic consecutive multiplex tissue staining method, was performed with a series of immune markers (Table), to characterize T cell subsets, B cells, macrophages, mature dendritic cells (DCs), and immune checkpoints on pre &amp; post NACT formalin-fixed paraffin-embedded tumor tissue sections. Density was calculated for each marker (+ve cells/mm 2 ) following annotation of tissues by tumor, fibrosis, necrosis, stromal &amp; tumor infiltrating lymphocyte-enriched areas. Results: Nine pts were enrolled. Final analysis included 5 pts with adequate tissue. Median age = 48 (41-56), with 4 female, 4 intrahepatic cholangiocarcinomas &amp; 1 gallbladder. All pts received Gemcitabine/Cisplatin as NACT with a median of 5 (4-7) cycles. Median time from diagnosis to surgery was 4.3 (1.4-7.8) months &amp; last cycle to surgery was 0.9 (0.6-1.5) month. All pts were MMR proficient, 1 Her2+ &amp; 2 with FGFR2 amplification. NACT on average produced a depletion of all immune markers (Table). Given the small N, each pt was considered their own control &amp; changes in mean cell densities post NACT were calculated. Pt2 with a 40-fold increase in PDL1 expression &amp; 5-fold decrease in CD8:FOXP3 ratio notably had the shortest disease-free interval (DFI). Pt3 with the longest DFI had the largest increase in CD8:FOXP3 by about 8-fold combined with a decrease in PDL1. Conclusions: Preliminary results suggest NACT may modulate immune microenvironment despite overall immune cell depletion. Future studies should focus on strategies to expand immune modulation of the tumor microenvironment in BTC by NACT, including immune oncology agent priming prior to or after NACT.[Table: see text]